Drug-Induced Micelle-to-Supermicelle Transition in Cetyltrimethylammonium Bromide (CTAB): Comparative Study with Acetylenic Gemini Surfactant via Experimental and DFT Approaches

Self-assembly or coassembly of amphiphiles creates a large number of aggregated structures, among which the supermicelle structure is very important for its unique morphology and versatile application in the nanotechnology and biomedicine fields. It is well-known that supermicelles with different morphologies can be created when amphiphilic block copolymers assemble hierarchically in a certain solvent. However, to the best of our knowledge, this study reports a rare example of supermicellar structure formation arising from the coassembly of a conventional surfactant (cetyltrimethylammonium bromide, CTAB) with an amphiphilic drug (sodium fenbufen). Here, a comprehensive list of supermicellar structures is reported, formed by the coassembly of the drug and CTAB, including spherical, linear, and cross-linked forms. TEM analysis, along with DLS, anisotropy, FESEM, and AFM measurements, supported the formation of the supermicellar structure. Along with supermicelle formation, we have also focused on the micellar property of the drug-surfactant mixed system. Here, we compared mixed micelle formation between the fenbufen drug with conventional CTAB and the synthesized acetylenic gemini surfactants (16–4–16). We have performed a DFT simulation study to understand the molecular interaction between drugs and surfactants. The interaction of gemini surfactant with drug molecules is much stronger than CTAB, according to DFT calculations. However, gemini surfactant micelles undergo structural reorganization into smaller mixed aggregates upon incorporation of drug molecules due to packing constraints and reduced structural flexibility. On the other hand, in CTAB micellar systems, drug-induced reduction of electrostatic repulsion promotes intermicellar association, leading to the formation of larger supermicellar aggregates with diverse morphologies. These supermicelle aggregates have a variety of uses in the biomedical field, drug delivery, nanotechnology, and other key disciplines.